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首页> 外文期刊>Molecular and Cellular Biology >Recombinant NFAT1 (NFATp) is regulated by calcineurin in T cells and mediates transcription of several cytokine genes.
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Recombinant NFAT1 (NFATp) is regulated by calcineurin in T cells and mediates transcription of several cytokine genes.

机译：重组NFAT1（NFATp）在T细胞中受钙调神经磷酸酶调节，并介导几种细胞因子基因的转录。

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Transcription factors of the NFAT family play a key role in the transcription of cytokine genes and other genes during the immune response. We have identified two new isoforms of the transcription factor NFAT1 (previously termed NFATp) that are the predominant isoforms expressed in murine and human T cells. When expressed in Jurkat T cells, recombinant NFAT1 is regulated, as expected, by the calmodulin-dependent phosphatase calcineurin, and its function is inhibited by the immunosuppressive agent cyclosporin A (CsA). Transactivation by recombinant NFAT1 in Jurkat T cells requires dual stimulation with ionomycin and phorbol 12-myristate 13-acetate; this activity is potentiated by coexpression of constitutively active calcineurin and is inhibited by CsA. Immunocytochemical analysis indicates that recombinant NFAT1 localizes in the cytoplasm of transiently transfected T cells and translocates into the nucleus in a CsA-sensitive manner following ionomycin stimulation. When expressed in COS cells, however, NFAT1 is capable of transactivation, but it is not regulated correctly: its subcellular localization and transcriptional function are not affected by stimulation of the COS cells with ionomycin and phorbol 12-myristate 13-acetate. Recombinant NFAT1 can mediate transcription of the interleukin-2, interleukin-4, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor promoters in T cells, suggesting that NFAT1 contributes to the CsA-sensitive transcription of these genes during the immune response.
机译：NFAT家族的转录因子在免疫应答过程中在细胞因子基因和其他基因的转录中起关键作用。我们已经确定了转录因子NFAT1的两个新亚型（以前称为NFATp），它们是在鼠和人T细胞中表达的主要亚型。当在Jurkat T细胞中表达时，重组NFAT1如预期的那样受到钙调蛋白依赖性磷酸酶钙调神经磷酸酶的调控，其功能被免疫抑制剂环孢菌素A（CsA）抑制。重组NFAT1在Jurkat T细胞中的反式激活需要用离子霉素和佛波醇12-肉豆蔻酸酯13-乙酸酯双重刺激。这种活性通过组成型活性钙调神经磷酸酶的共表达得到增强，并被CsA抑制。免疫细胞化学分析表明，重组NFAT1定位于瞬时转染的T细胞的细胞质中，并在离子霉素刺激后以CsA敏感的方式转运到细胞核中。但是，当在COS细胞中表达时，NFAT1能够进行反式激活，但调控不正确：用离子霉素和12-肉豆蔻酸佛波醇13-乙酸盐刺激COS细胞不会影响其亚细胞定位和转录功能。重组NFAT1可以介导T细胞中白细胞介素2，白细胞介素4，肿瘤坏死因子α和粒细胞巨噬细胞集落刺激因子启动子的转录，这表明NFAT1在免疫应答过程中有助于这些基因的CsA敏感转录。 。

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